ReviewJournal of cardiovascular pharmacology2014
Zinc and the prooxidant heart failure phenotype.
Review in Journal of cardiovascular pharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
17 citing papers in PubMed, 1 synthesis or guideline pooled it, 39 citations in OpenAlex.
- The Relationship between Serum Zinc Level and Heart Failure: A Meta-Analysis.BioMed research international · 2018Pooled it
- Zinc-Mediated Defenses Against Toxic Heavy Metals and Metalloids: Mechanisms, Immunomodulation, and Therapeutic Relevance.International journal of molecular sciences · 2025Review
- Mortality and cardiorenal outcomes among heart failure patients with zinc deficiency: a multicenter retrospective cohort study of 8,290 patients.Frontiers in nutrition · 2025Article
- An Overexpression of SLC30A6 Gene Contributes to Cardiomyocyte Dysfunction via Affecting Mitochondria and Inducing Activations in K-Acetylation and Epigenetic Proteins.Biochemical genetics · 2024Article
- Serum zinc concentration in patients with myocardial infarction: a retrospective study.BMC cardiovascular disorders · 2024Article
- Contaminant Metals and Cardiovascular Health.Journal of cardiovascular development and disease · 2023Review
- Myocardial TRPC6-mediated ZnNature communications · 2022Article
- Micronutrient deficiencies in heart failure: Mitochondrial dysfunction as a common pathophysiological mechanism?Journal of internal medicine · 2022Review
- The Oxidative Balance Orchestrates the Main Keystones of the Functional Activity of Cardiomyocytes.Oxidative medicine and cellular longevity · 2022Review
- Friend or Foe? The Roles of Antioxidants in Acute Lung Injury.Antioxidants (Basel, Switzerland) · 2021Review
- Association between Reduced Serum Zinc and Diastolic Dysfunction in Maintenance Hemodialysis Patients.Nutrients · 2021Article
- The role of labile ZnMolecular and cellular biochemistry · 2021Review
- Zinc Deficiency as a Reversible Cause of Heart Failure.Texas Heart Institute journal · 2020Article
- Zinc deficiency and cellular oxidative stress: prognostic implications in cardiovascular diseases.Acta pharmacologica Sinica · 2018Review
- Induction of endoplasmic reticulum stress and changes in expression levels of ZnMolecular and cellular biochemistry · 2018Article
- Critical Role of Zinc as Either an Antioxidant or a Prooxidant in Cellular Systems.Oxidative medicine and cellular longevity · 2018Review
- Impact of Labile Zinc on Heart Function: From Physiology to Pathophysiology.International journal of molecular sciences · 2017Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Neurohormonal activation with attendant aldosteronism contributes to the clinical appearance of congestive heart failure (CHF). Aldosteronism is intrinsically coupled to Zn and Ca dyshomeostasis, in which consequent hypozincemia compromises Zn homeostasis and Zn-based antioxidant defenses that contribute to the CHF prooxidant phenotype. Ionized hypocalcemia leads to secondary hyperparathyroidism with parathyroid hormone-mediated Ca overloading of diverse cells, including cardiomyocytes. When mitochondrial Ca overload exceeds a threshold, myocyte necrosis follows. The reciprocal regulation involving cytosolic free [Zn]i as antioxidant and [Ca]i as prooxidant can be uncoupled in favor of Zn-based antioxidant defenses. Increased [Zn]i acts as a multifaceted antioxidant by: (1) inhibiting Ca entry through L-type channels and hence cardioprotectant from the Ca-driven mitochondriocentric signal-transducer effector pathway to nonischemic necrosis, (2) serving as catalytic regulator of Cu/Zn-superoxide dismutase, and (3) activating its cytosolic sensor, metal-responsive transcription factor that regulates the expression of relevant antioxidant defense genes. Albeit present in subnanomolar range, increased cytosolic free [Zn]i enhances antioxidant capacity that confers cardioprotection. It can be achieved exogenously by ZnSO4 supplementation or endogenously using a β3-receptor agonist (eg, nebivolol) that enhances NO generation to release inactive cytosolic Zn bound to metallothionein. By recognizing the pathophysiologic relevance of Zn dyshomeostasis in the prooxidant CHF phenotype and by exploiting the pharmacophysiologic potential of [Zn]i as antioxidant, vulnerable cardiomyocytes under assault from neurohormonal activation can be protected and the myocardium spared from adverse structural remodeling.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.